As is well-known in the pharmaceutical industry, in order to establish the safety and efficacy of a drug, as well as the most therapeutic dosage thereof, it is necessary to establish the specific pharmacokinetics and metabolism associated with such drug when the same is administered to a patient via clinical pharmacology. In this respect, due to the tendencies of different compounds to be absorbed at varying rates, achieve varying peak serum concentrations, and become metabolized and excreted via one or more metabolic pathways, proper formulation is crucial to insure that an administered dosage of a given pharmaceutical composition is neither excessive, so as to cause possible adverse side effects or toxicity, nor below certain threshold concentrations, such that the composition fails to produce the desired therapeutic benefit.
To establish such parameters, detailed and exhaustive in vivo (in animals) and in vitro studies are conducted to obtain data on pharmaceutical safety and efficacy in order to demonstrate that there will be no unreasonable hazard in initiating trials in human beings. The rate and extent of absorption and excretion of a given compound are usually determined during the course of the subacute toxicity studies by following changes in plasma concentration of the pharmaceutical composition after oral and parenteral administration. Additionally, organs and tissues may have to be analyzed directly for their content of the pharmaceutical composition, as well as any sub-components or metabolites thereof.
To the extent toxicity and efficacy can be sufficiently evaluated, further tests are necessary to determine preferred formulations of the commercial pharmaceutical composition product to be used in treating patients. These formulation considerations are particularly sensitive where pharmaceutical manufacturers strive to produce formulations of pharmaceutical compositions that may be administered in daily doses. In this respect, it is known that pharmaceutical compositions administered daily achieve the highest degree of patient compliance and acceptance, as opposed to pharmaceutical formulations requiring administration two or more times a day or every other day. As is well-known, however, to provide for such precise dosing requires meticulous analysis and formulation such that a particular dosage coincides with a sufficient degree of absorption, distribution and bioavailability within a sufficiently large cross-section of the population so as to produce the desired therapeutic benefit.
While protocols have been established for evaluating the clinical pharmacology of so-called "ethical" pharmaceutical compositions, such standards currently do not apply for herbal remedies or plant extracts that, although not supported by clinical data, are believed to produce significant therapeutic benefits for a variety of conditions. As a consequence, no established standards for clinical testing procedures currently exist, let alone the formulations or dosages of a given composition that are believed to be universally accepted as the preferred dosage ranges. In this regard, most herbal remedy compositions sold in this country merely use powdered whole herb or occasionally standardized extracts obtained from companies that may or may not have completed clinical trials on the extracts, or sell the extracts as prescription drugs in one or more foreign countries. In cases where such standardized extracts are not available, manufacturers tend to obtain extracts from high-quality suppliers and rely solely upon the quality control measures implemented thereby to insure uniform concentrations of such active ingredients.
Such manufacturing procedures, however, are ill-suited in pharmaceutical composition manufacturing practices insofar as such practices tend to be unreliable, which consequently results in the production of pharmaceutical compositions that contain too much or not enough of the active ingredient necessary to bring about the therapeutic benefit. Moreover, even to the extent the active ingredient in a given herbal remedy or plant extract is present in an optimal concentration necessary to produce a given therapeutic benefit, how such active ingredient is ultimately formulated with other ingredients, such as an excipient that slows the absorption of such active ingredient, or how such active ingredient reacts to a manufacturing process, such as mixing which potentially destroys the biologically active form of the active ingredient, yet further thwarts the ability of such formulations to uniformly and consistently impart the desired therapeutic benefit.
These threats extend across all lines of pharmaceutical manufacturing practices, whether it be in making tablets, lozenges, liquid suspensions or gel-suspension caplets. Moreover, such threats are compounded further to the extent the active ingredient of such herbal remedy or plant extract comprises a multi-component botanical, the extracts of which are collectively believed to produce a desired therapeutic benefit. However, substantial difficulty occurs when trying to formulate, let alone standardize, herbal extracts that possess the necessary active ingredients, as well as their respective concentrations.
Accordingly, there is a need in the art for a system and method by which pharmaceutical compositions, and in particular herbal remedies and plant extracts, can be evaluated for absorption properties for use in deriving standardized formulations and/or extracts thereof. There is additionally a need in the art for a method for determining the absorption properties of herbal remedies and plant extracts that can reliably reproduce the rate by which the same are absorbed into the human body and the resultant serum concentrations achieved thereby, particularly when the same are administered orally, to thus enable such extract formulations to be standardized. There is yet a further need in the art for a method for determining the absorption rates of herbal remedies and plant extracts that is simple to construct, utilizes relatively inexpensive materials, and is based upon accepted principles and parameters for establishing drug absorption activity using biological absorption models.